Indapamide - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 143.0 mg, corn starch 1.5 mg, povidone (polyvinylpyrrolidone low molecular weight) 2.0 mg, sodium lauryl sulfate 0.5 mg, calcium stearate 0.5 mg.

The weight of the contents of the capsule is 150.0 mg.

Capsules, hard gelatin: body - titanium dioxide (2%), gelatin (up to 100%); lid - titanium dioxide (2%), dye azorubin (0.0328%), dye sunset yellow (0.219%), gelatin (up to 100%).

The weight of the capsule is 198.0 mg.

Description:

Hard gelatin capsules No. 3 with a white body and an orange lid. The contents of the capsules are a powder or compacted mass of white or white with a yellowish tint of color,decaying when pressed with a glass rod.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide refers to sulfonamide derivatives with an indole ring and by pharmacological properties is similar to thiazide diuretics that inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. This increases the release of kidney ions of sodium, chlorine and, to a lesser extent, the ions of potassium and magnesium, which is accompanied by an increase in diuresis and antihypertensive effect.

Indapamide reduces the tone of the smooth muscles of the arteries and has a vasodilating effect, reduces the overall peripheral resistance of the vessels. These effects are mediated by a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; increased synthesis prostaglandin E2, possessing vasodilator activity; suppression of calcium current in smooth muscle cells of blood vessels.

Indapamide reduces the hypertrophy of the left ventricle of the heart.

Indapamide in monotherapy in doses that do not cause a pronounced diuretic effect, has a 24-hour antihypertensive effect.Antihypertensive activity of indapamide is associated with improving the elastic properties of large arteries, reducing arteriolar and general peripheral vascular resistance. Indapamide reduces left ventricular hypertrophy.

Thiazide and thiazide-like diuretics achieve a therapeutic effect at a certain dose, while the incidence of side effects continues to increase with a further increase in the dose of the drug. Therefore, do not increase the dose of the drug, if the recommended dose does not achieve a therapeutic effect.

In short, medium duration and long-term studies involving patients with hypertension, it was shown that indapamide:

- does not affect the lipid metabolism, including the level of triglycerides, cholesterol, low-density lipoproteins and high-density lipoproteins;

- does not affect the metabolism of carbohydrates, including in patients with diabetes mellitus.

Pharmacokinetics:

Suction

The released indapamide quickly and completely absorbed in the gastrointestinal tract.Food intake slightly increases the absorption time of indapamide, without affecting the completeness of absorption. The maximum concentration in blood plasma is achieved 1-2 hours after ingestion of a single dose of 2.5 mg. At new mountain receptions fluctuations of concentration of an indapamide in a blood plasma in an interval between receptions of a preparation are smoothed out. There is an individual variability in indapamide absorption indices.

Distribution

About 79% of indapamide binds to proteins of the plasma of the kropi and, due to the presence of a high affinity for elastin, is concentrated in the smooth muscles of the vascular walls. It also combines with the erythrocyte carboxyhydrase without inhibiting the activity of this enzyme.

The half-life is 14-24 hours (on average, 18 hours). The equilibrium concentration is achieved after 7 days of taking the drug. When you re-take the drug is not observed its cumulation.

Metabolism and excretion

Indapamide is metabolized in the liver and is excreted as inactive metabolites, mainly by the kidneys (60-80% of the dose taken) and through the intestine (22%). He More than 5% of indapamide is excreted from the body by the kidneys in unchanged form.

Pharmacokinetics in specific patient groups

In patients with renal insufficiency, the pharmacokinetics of the drug Indapamide does not change.

Indications:Arterial hypertension.

Contraindications:

- Hypersensitivity to indapamide, other derivatives of sulfonamide or other components of the drug;

- severe renal failure (creatinine clearance (CK) less than 30 ml / min);

- anuria;

- severe hepatic insufficiency (including with encephalopathy);

- hypokalemia;

- pregnancy;

- the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

- Impaired liver and / or kidney function (QC more than 30 ml / min);

- violation of water and electrolyte balance;

- diabetes;

- chronic heart failure (CHF);

- hyperparathyroidism;

- hyperuricemia and gout;

- elderly age;

- patients with an increased interval QT on ECG, weakened patients or patients receiving concomitant therapy, as a result of which an extension of the interval QT (see the section "Interaction with other medicinal products").

Pregnancy and lactation:

Pregnancy

As a rule, during pregnancy, diuretic drugs should not be prescribed. Do not use these drugs to treat physiological swelling in pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development.

Breastfeeding period

It is not recommended to prescribe a drug Indapamide nursing mothers (indapamide excreted in breast milk). If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake.

Take the drug preferably in the morning, without chewing, squeezed with enough liquid.

With arterial hypertension, the drug Indapamide is prescribed in a dose of 2.5 mg (1 capsule) once a day. If after 4-8 weeks of treatment the desired therapeutic effect is not achieved, the dose of the drug should not be increased (the risk of side effects increases without increasing the antihypertensive effect). Instead, it is recommended that another antihypertensive agent be included in the treatment regimen, not which is a diuretic.In the case of starting treatment with two antihypertensive drugs, the dose of the drug Indapamide remains equal to 2.5 mg once in the morning.

When severe hepatic impairment (including with encephalopathy) drug intake Indapamide contraindicated (see section "Contraindications").

In severe renal failure (CC less than 30 ml / min) drug intake Indapamide contraindicated (see section "Contraindications").

In the treatment of elderly patients, the threshold value of creatinine concentration in the blood plasma varies depending on age, body weight and gender.

To patients of advanced age a drug Indapamide can be used only with normal kidney function or with minor impairment of kidney function.

Side effects:

Classification of the incidence of adverse events according to the recommendations of the World Health Organization (WHO):

very often> 1/10;

often from> 1/100 to <1/10;

infrequently from> 1/1000 to <1/100;

rarely from> 1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

frequency is unknown - according to available data, it is possible to establish the frequency of occurrence of ns.

From the side of the circulatory and lymphatic systems:

very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system:

infrequently - lethargy, feelings of anxiety, increased motor activity;

rarely - asthenia, headache, paresthesia, vertigo, dizziness;

frequency unknown - faint.

From the side of the cardiovascular system:

very rarely - arrhythmia, marked decrease in blood pressure, orthostatic hypotension;

frequency unknown - arrhythmia of the "pirouette" type (possibly fatal) (see "Interactions with other medicinal products" and "Special instructions").

From the digestive system:

infrequently - vomiting;

rarely - nausea, constipation, dryness of the oral mucosa;

very rarely - pancreatitis.

From the urinary system:

very rarely - kidney failure.

From the liver and biliary tract:

very rarely - a violation of liver function;

frequency unknown - the possibility of developing hepatic encephalopathy in the case of liver failure (see the sections "Contraindications" and "Special instructions"), hepatitis.

From the skin and subcutaneous fat:

reactions of hypersensitivity, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions:

often - maculopapular rash;

infrequently - hemorrhagic vasculitis;

very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome;

frequency is unknown - in patients with acute form of systemic lupus erythematosus, the course of the disease may worsen.

Individual cases of photosensitivity reactions are described (see section "Special instructions").

Laboratory indicators:

very rarely - hypercalcemia;

frequency unknown - interval increase QT on the ECG (see section "Special instructions"), increasing the concentration of uric acid and glucose in the crayfish (thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes mellitus), increased activity of "liver" transaminases, a decrease in the content of potassium ions and development of hypokalemia, especially significant for patients at risk (see section "Special instructions"); hyponatremia accompanied by hypovolemia,dehydration and orthostatic hypotension (simultaneous hypochloraemia can lead to metabolic alkalosis of compensatory nature (the probability and severity of this effect is low)).

Overdose:

Indapamide even in very high doses (up to 40 mg, that is 27 times more than the therapeutic dose) does not have a toxic effect.

Symptoms

Signs of acute drug poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Symptoms of overdose may include nausea, vomiting, severe lowering of blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria, or oliguria, leading to anuria (due to hypovolemia).

Treatment

Emergency measures are limited to removing the drug from the body: gastric lavage and / or the appointment of activated charcoal, followed by the restoration of the water-electrolyte balance.

There is no specific antidote.

Interaction:

Lithium preparations

With simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose.If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.

Combinations of drugs that require special attention

Drugs that can cause arrhythmia such as "pirouette":

- antiarrhythmic drugs: IА class (quinidine, hydroquinidine, disopyramide), Class III (amiodarone, dofetilide, ibutilide), sotalol;

- some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

- others: beprideil, cisapride, difemannil, erythromycin (intravenously), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (intravenously).

Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (risk factor - hypokalemia).

It is necessary to determine the content of potassium ions in the blood plasma and, if necessary, adjust it before the start of combination therapy with indapamide and the above drugs.It is necessary to monitor the clinical condition of the patient, control the content of plasma electrolytes, ECG parameters.

Patients with hypokalemia should use drugs that do not cause arrhythmia such as "pirouette".

Non-steroidal anti-inflammatory drugs (for systemic administration), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of acetylsalicylic acid (≥ 3 g / day)

It is possible to reduce the antihypertensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration rate). Patients need to compensate for fluid loss. At the beginning of treatment, the function of the kidneys should be carefully monitored.

Angiotensin converting enzyme (ACE) inhibitors

The administration of ACE inhibitors to patients with a reduced content of sodium ions in the blood (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure.

Patients with arterial hypertension and, possibly, reduced due to the intake of diuretics with the content of sodium ions in blood plasma should:

- 3 days before the start of treatment with an ACE inhibitor, stop taking diuretics; in the future, if necessary, the reception of diuretics can be resumed;

- or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose if necessary.

In CHF, treatment with ACE inhibitors should begin with low doses with a possible preliminary reduction in the dose of diuretics.

In all cases, in the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (creatinine concentration in the blood plasma).

Other drugs, capable of causing hypokalemia: amphotericin B (intravenously), gluco- and mineralocorticosteroids (for systemic administration), tetracosactide, laxatives, stimulating bowel motility

Increased risk of hypokalemia (additive effect). It is necessary to constantly monitor the content of potassium ions in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.

Baclofen

There is an increase in anti-hypertensive effect.Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium ions in the blood plasma, the parameters of the ECG, and, if necessary, adjust the therapy should be monitored.

Combinations of medicines requiring attention

Potassium-sparing diuretics (amiloride, spironolactone, eplerenone, triamterene)

Combination therapy with indapamide and potassium-sparing diuretics is advisable in some Nazis, but in this casee the possibility of developing hypokalemia (especially in patients with diabetes mellitus and patients with renal insufficiency) or hyperkalemia is excluded.

It is necessary to control the content of potassium ions in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

Metformin

Functional renal failure, which can occur against the background of diuretics, especially "loop", with the simultaneous appointment of metformin increases the risk of lactic acidosis.

Do not use metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing contrast agents

Dehydration of the body against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Before using iodine-containing contrast agents, patients must compensate for fluid loss.

Tricyclic antidepressants, antipsychotics (antipsychotics)

Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Salts of calcium

With simultaneous administration, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

Cyclosporin, tacrolimus

It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal content of liquid and sodium ions.

Corticosteroids, tetracosactide (with system assignment)

Reduction of antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Special instructions:

Dysfunction of the liver

In the appointment of thiazide and thiazide-like diuretics in patients with impaired hepatic function, it is possible to develop hepatic encephalopathy, especially in the case of disturbance of the water-electrolyte balance. In this case, the taking of diuretics should be stopped immediately.

Photosensitivity

Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported (see the "Side effect" section). In the case of developing photosensitivity reactions against the background of taking the drug should stop treatment.

If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance

Content of sodium ions in blood plasma

Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure.All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to regularly monitor the content of sodium ions, since initially the decrease in the content of sodium ions in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most thorough control of the sodium ion content is indicated in patients with cirrhosis of the liver and elderly people (see the "Side effect" and "Overdose" sections)

The content of potassium ions in the blood plasma

In therapy with thiazide and thiazide-like diuretics, the main risk is a sharp decrease in the content of potassium ions in the blood plasma and the development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (<3.4 mmol / l) in patients of the following categories: elderly patients who are weakened or are receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the interval QT, patients with cirrhosis of the liver, peripheral edema or ascites, ischemic heart disease, heart failure. Hypokalemia in such patients increases the toxic effect of cardiac glycosides and increases the riskdevelopment of arrhythmias.

In addition, the high-risk group includes patients with an increased interval QT, it does not matter whether this increase is due to innate causes or effects of drugs.

Hypokalemia, as well as bradycardia, is a condition that promotes the development of severe arrhythmias and, especially, pirouette-type arrhythmias, which can lead to death. In all the cases described above, it is necessary to regularly monitor the content of potassium ions in the blood plasma. The first measurement of the content of potassium ions in the blood plasma should be carried out within the first week after the start of treatment.

When hypokalemia occurs, appropriate treatment should be prescribed.

The content of calcium ions in the blood plasma

It should be borne in mind that thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium ions in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

It is necessary to cancel the reception of diuretic drugs before the study of the function of parathyroid glands.

The concentration of glucose in the blood plasma

It is necessary to monitor the concentration of glucose in blood plasma in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Patients with gout may increase the incidence of attacks or exacerbate the course of gout.

Diuretic drugs and kidney function

Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg / L, or 220 μmol / L). In elderly patients, the normal concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.

It should be borne in mind that at the beginning of treatment, patients may experience a decrease in the glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the kidney function is not impaired, such a temporary functional kidney failure, as a rule, passes without consequences,However, with the existing renal failure, the patient's condition may worsen.

Athletes

Indapamide can give a positive result in the conduct of doping control.

Effect on the ability to drive transp. cf. and fur:

At the beginning of treatment with the drug Indapamide should refrain from driving motor vehicles and practicing potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as it may lead to dizziness.

Form release / dosage:

Capsules, 2.5 mg.

Packaging:

10 or 14 capsules in a planar cell package.

1, 2, 3, 5 or 6 contour cell packs of 10 capsules.

1, 2, 3 or 4 contour packs of 14 capsules together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N003774 / 01

Date of registration:03.12.2009 / 13.09.2016

Expiration Date:Unlimited

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Representation: & nbspVERTEKS CJSC VERTEKS CJSC Russia

Information update date: & nbsp03.11.2017

Illustrated instructions

Instructions

Indapamide (Indapamide)